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During early pregnancy in mice, the establishment of uterine receptivity and endometrial decidualization require the extensive proliferation and differentiation of endometrial epithelial cells or stromal cells. Pin1 has been suggested to act as a molecular 'timer' of the cell cycle and is involved in the regulation of cellular proliferation and differentiation by binding many cell-cycle regulatory proteins. However, its physiological role during early pregnancy is still not fully understood. Here, we employed immunohistochemistry to determine the spatiotemporal pattern of Pin1 expression during early pregnancy. We found that Pin1 was mainly localized in subluminal stromal cells on day 4, in the decidual zone on days 5 to 8 of pregnancy and in artificial decidualization. Using a uterine stromal cell culture system, we found that progesterone, but not estrogen, induced the expression of Pin1 in a progesterone receptor-dependent manner. Inhibition of Pin1 in the uterus leads to impaired embryo implantation and decidualization in mice. Notably, a decrease in Pin1 activation affected the functional execution of several implantation- or decidualization-related factors. These findings provide new evidence for a previously unknown function of Pin1 in mediating embryo implantation and decidualization during successful pregnancy establishment and maintenance.
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Decidua , Implantación del Embrión , Peptidilprolil Isomerasa de Interacción con NIMA , Útero , Animales , Femenino , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Implantación del Embrión/fisiología , Ratones , Embarazo , Decidua/metabolismo , Decidua/citología , Útero/metabolismo , Útero/citología , Progesterona/metabolismo , Células del Estroma/metabolismo , Receptores de Progesterona/metabolismo , Células Cultivadas , Endometrio/metabolismo , Endometrio/citologíaRESUMEN
Methanol is a promising hydrogen carrier for fuel cell vehicles (FCVs) via methanol steam reforming (MSR) reaction. Ceria supported copper catalyst has attracted extensive attentions due to the extraordinary oxygen storage capacity and abundant oxygen vacancies. Herein, we developed a colloidal solution combustion (CSC) method to synthesize a porous Cu/CeO2(CSC) catalyst. Compared with Cu/CeO2 catalysts prepared by other methods, the Cu/CeO2(CSC) catalyst possesses highly dispersed copper species and abundant Cu+-Ov-Ce3+ sites at the copper-ceria interface, contributing to methanol conversion of 66.3 %, CO2 selectivity of 99.2 %, and outstanding hydrogen production rate of 490 mmol gcat-1 h-1 under 250 °C. The linear correlation between TOF values and Cu+-Ov-Ce3+ sites amount indicates the vital role of Cu+-Ov-Ce3+ sites in MSR reaction, presenting efficient ability in activation of water. Subsequently, a deep understanding of CSC method is further presented. In addition to serving as a hard template, the colloidal silica also acts as disperser between nanoparticles, enhancing the copper-ceria interactions and facilitating the generation of Cu+-Ov-Ce3+ sites. This study offers an alternative approach to synthesize highly dispersed supported copper catalysts.
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Novel carbonyl-N embedded hetero[7]helicene diastereomers incorporating axially chiral binaphthyl were facilely synthesized and separated. The separated homochiral hetero[7]helicenes exhibit intense green photoluminescence and circularly polarized luminescence (CPL) with luminescence dissymmetry factors (glum) of 1.4 × 10-3 due to the intrinsic helical multiple-resonance skeleton.
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BACKGROUND: Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD. METHODS: Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package "Bibiometrix," SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data. RESULTS: A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research. CONCLUSION: By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.
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Bibliometría , Enfermedad de Boca, Mano y Pie , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , Investigación Biomédica/estadística & datos numéricos , Investigación Biomédica/tendenciasRESUMEN
PURPOSE: Sunitinib is a recommended drug for metastatic renal cell carcinoma (RCC). However, the therapeutic potential of sunitinib is impaired by toxicity and resistance. Therefore, we seek to explore a combinatorial strategy to improve sunitinib efficacy of low-toxicity dose for better clinical application. METHODS: We screen synergistic reagents of sunitinib from a compound library containing 1374 FDA-approved drugs by in vitro cell viability evaluation. The synergistically antiproliferative and proapoptotic effects were demonstrated on in vitro and in vivo models. The molecular mechanism was investigated by phosphoproteomics, co-immunoprecipitation, immunofluorescence and western-blot assays, etc. RESULTS: From the four-step screening, nilotinib stood out as a potential synergistic killer combined with sunitinib. Subsequent functional evaluation demonstrated that nilotinib and sunitinib synergistically inhibit RCC cell proliferation and promote apoptosis in vitro and in vivo. Mechanistically, nilotinib activates E3-ligase HUWE1 and in combination with sunitinib renders MCL-1 for degradation via proteasome pathway, resulting in the release of Beclin-1 from MCL-1/Beclin-1 complex. Subsequently, Beclin-1 induces complete autophagy flux to promote antitumor effect. CONCLUSION: Our findings revealed that a novel mechanism that nilotinib in combination with sunitinib overcomes sunitinib resistance in RCC. Therefore, this novel rational combination regimen provides a promising therapeutic avenue for metastatic RCC and rationale for evaluating this combination clinically.
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Autofagia , Carcinoma de Células Renales , Resistencia a Antineoplásicos , Neoplasias Renales , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Pirimidinas , Sunitinib , Sunitinib/farmacología , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Humanos , Autofagia/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Línea Celular Tumoral , Animales , Pirimidinas/farmacología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Ratones Desnudos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Ratones Endogámicos BALB C , Proteolisis/efectos de los fármacos , Beclina-1/metabolismoRESUMEN
RAGE is a multiligand receptor for the immunoglobulin superfamily of cell surface molecules and is expressed in Müller cells, vascular endothelial cells, nerve cells and RPE cells of the retina. Diabetic retinopathy (DR) is a multifactorial disease associated with retinal inflammation and vascular abnormalities and is the leading cause of vision loss or impairment in older or working-age adults worldwide. Therapies aimed at reducing the inflammatory response and unnecessary angiogenesis can help slow the progression of DR, which in turn can save patients' vision. To maximize the efficacy and minimize the side effects, treatments that target key players in the pathophysiological process of DR need to be developed. The interaction between RAGE and its ligands is involved in a variety of cytopathological alterations in the retina, including secretion of inflammatory factors, regulation of angiogenesis, oxidative stress, structural and functional changes, and neurodegeneration. In this review, we will summarize the pathologic pathways mediated by RAGE and its ligand interactions and discuss its role in the progression of diabetic retinopathy to explore potential therapeutic targets that are effective and safe for DR.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Anciano , Células Endoteliales/metabolismo , Retina , Inflamación , Neuronas , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologíaRESUMEN
To accurately and efficiently predict the molecular response properties (such as polarizability) at post-Hartree-Fock levels for condensed-phase systems under periodic boundary conditions (PBC) is still an unaccomplished and ongoing task. We demonstrate that static isotropic polarizabilities can be cost-effectively predicted at post-Hartree-Fock levels by combining the linear-scaling generalized energy-based fragmentation (GEBF) and information-theoretic approach (ITA) quantities. In PBC-GEBF, the total molecular polarizability of an extended system is obtained as a linear combination of the corresponding quantities of a series of small embedded subsystems of several monomers. Here, we show that in the PBC-GEBF-ITA framework, one can obtain the molecular polarizabilities and establish linear relations to ITA quantities. Once these relations are established for smaller subsystems, one can predict the polarizabilities of larger subsystems directly from the molecular wavefunction (or electron density) via ITA quantities. Alternatively, one can determine the total molecular polarizability via a linear combination equation in PBC-GEBF. We have corroborated that this newly proposed PBC-GEBF-ITA protocol is much more efficient than the original PBC-GEBF approach but is not much less accurate and that this conclusion holds for both many-body perturbation theory and the coupled cluster calculations. Good efficiency and transferability of the PBC-GEBF-ITA protocol are demonstrated for periodic systems with several hundred atoms in a unit cell.
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Chiral macrocycles with circularly polarized luminescence (CPL) have attracted increasing attention due to the rigid structure, symmetrical chiral geometry and large luminescence dissymmetry factors (glum ). However, most chiral macrocycles are more emissive in solutions but have weakened fluorescence quantum yields (ΦF ) in aggregates, limiting their further application. In this paper, chiral macrocycle R/S-PhTPE was synthesized by combining chiral macrocycle architectonics with Z-o-phenyltetraphenylethylene (PhTPE) foldamer. Enhanced solution state emission and characteristic aggregation enhanced emission (AEE) effect can be observed for R/S-PhTPE due to the folded PhTPE conformation. Macrocycle immobilization and folded conformation endow PhTPE moiety with stable helical conformation. Most importantly, R/S-PhTPE exhibits opposite CPL signals compared with common chiral TPEs, demonstrating the evident impact of folded conformation. This work reports the first and deep insights into the chiroptical properties of chiral PhTPE foldamers, and will provide a new strategy to tune ΦF and CPL signals of AIE active chiral macrocycles.
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PURPOSE: Polyamine modulating factor 1 binding protein (PMFBP1) acts as a scaffold protein for the maintenance of sperm structure. The aim of this study was further to identify the new role and molecular mechanism of PMFBP1 during mouse spermatogenesis. METHODS AND RESULTS: We identified a profile of proteins interacting with PMFBP1 by immunoprecipitation combined with mass spectrometry and demonstrated that class I histone deacetylases, particularly HDAC3 and chaperonin-containing TCP1 subunit 3 (CCT3), were potential interaction partners of PMFBP1 based on network analysis of protein-protein interactions and co-immunoprecipitation. Immunoblotting and immunochemistry assays showed that loss of Pmfbp1 would result in a decline in HDACs and change the proteomic profile of mouse testis, in which differently expressed proteins are associated with spermatogenesis and assembly of flagella, which was proved by proteomic analysis of testis tissue obtained from Pmfbp1-/- mice. After integrating with transcriptome data for Hdac3-/- and Sox30-/- round sperm obtained from a public database, RT-qPCR confirmed ring finger protein 151 (Rnf151) and ring finger protein 133 (Rnf133) were key downstream response factors of the Pmfbp1-Hdac axis affecting mouse spermatogenesis. CONCLUSION: Taken together, this study indicates a previously unidentified molecular mechanism of PMFBP1 in spermatogenesis whereby PMFBP1 interacts with CCT3, affecting the expression of HDAC3, followed by the downregulation of RNF151 and RNF133, resulting in an abnormal phenotype of sperm beyond the headless sperm tails. These findings not only advance our understanding of the function of Pmfbp1 in mouse spermatogenesis but also provide a typical case for multi-omics analysis used in the functional annotation of specific genes.
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Proteómica , Semen , Animales , Masculino , Ratones , Proteínas del Citoesqueleto/genética , Proteínas/metabolismo , Espermatogénesis/genética , Espermatozoides/metabolismo , Testículo/metabolismo , Ubiquitina-Proteína LigasasRESUMEN
The discovery of active constituents from food plants is an important area of research in pharmaceutical sciences. Aralia echinocaulis is a medicinal food plant that is mainly used to prevent or treat rheumatoid arthritis in China. This paper reported the isolation, purification and bioactivity of a polysaccharide (HSM-1-1) from A. echinocaulis. Its structural features were analyzed according to the molecular weight distribution, monosaccharide composition, gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectra. The results indicated that HSM-1-1 was a new 4-O-methylglucuronoxylan mainly composed of xylan and 4-O-methyl glucuronic acid with the molecular weight of 1.6 × 104 Da. Furthermore, the antitumor and anti-inflammatory activities of HSM-1-1 in vitro were investigated, and the results showed that HSM-1-1 had potent proliferation inhibition activity on colon cancer cell SW480 with an inhibition rate of 17.57 ± 1.03 % at a concentration of 600 µg/mL, as measured via MTS methods. To our knowledge, this is the first report of a polysaccharide structure obtained from A. echinocaulis and its bioactivities, and its potential as an adjuvant natural product with antitumor effects is shown.
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Aralia , Xilanos , Xilanos/farmacología , Xilanos/química , Aralia/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectroscopía de Resonancia Magnética , Polisacáridos/farmacologíaRESUMEN
Bioluminogenic probes emerged as powerful tools for imaging and analysis of various bioanalyses, but traditional approaches would be limited to the low sensitivity during determine the low activity of protease in clinical specimens. Herein, we proposed a caged luciferase inhibitor-based bioluminescence-switching strategy (CLIBS) by using a cleavable luciferase inhibitor to modulate the activity of luciferase reporter to amplify the detective signals, which led to the enhancement of detection sensitivity, and enabled the determination of circulating Aminopeptidase N (APN) activity in thousands of times diluted serum. By applying the CLIBS to serum samples in non-small cell lung cancer (NSCLC) patients from two clinical cohorts, we revealed that, for the first time, higher circulating APN activities but not its concentration, were associated with more NSCLC metastasis or higher metastasis stages by subsequent clinical analysis, and can serve as an independent factor for forecasting NSCLC patients' risk of metastasis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígenos CD13 , LuciferasasRESUMEN
OBJECTIVES: To evaluate the imaging quality of a synthetic phase-sensitive inversion recovery (SyPSIR) vessel and to add value to T2-weighted imaging (T2WI) for extramural venous invasion (EMVI) detection in patients with rectal cancer. METHODS: Participants in this retrospective study underwent preoperative synthetic MRI between October 2020 and April 2022. SyPSIR image reconstruction was performed with a single inversion time of 10 ms. A junior and a senior radiologist evaluated the imaging quality, including overall imaging quality scores, motion artifact scores, and relative image signal intensity contrast between the tumor and peritumoral vessels (SItumor-vessel), of both T2WI and SyPSIR vessels. Differences in imaging quality between the two methods were assessed using the Wilcoxon signed-rank test and two-sample t-test. EMVI scores were recorded for T2WI and T2WI+SyPSIR vessel. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic performance. RESULTS: A total of 106 patients (35 EMVI+ and 71 EMVI-) were evaluated. There were no statistically significant differences in the overall image quality scores, motion artifacts, or SItumor-vessel (p = 0.08-0.93) between the T2WI and SyPSIR vessels. On combining T2WI and SyPSIR vessels, the AUC for pathological EMVI+ diagnoses increased from 0.65 to 0.88 for the junior radiologist and from 0.86 to 0.96 for the senior radiologist. Furthermore, the sensitivity of the analyses by junior and senior radiologists increased from 0.40 to 0.77 and 0.49 to 0.86, respectively. CONCLUSION: A SyPSIR vessel can provide additional information to improve the diagnostic efficiency of pathological EMVI in rectal cancer, which may be beneficial for individualized clinical treatment. KEY POINTS: ⢠SyPSIR vessel and T2WI had similar imaging quality. ⢠EMVI evaluation in SyPSIR vessel has a high inter-observer agreement. ⢠The SyPSIR vessel has the potential to improve the diagnostic efficiency of EMVI detection in rectal cancer.
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Neoplasias del Recto , Humanos , Estudios Retrospectivos , Invasividad Neoplásica/patología , Neoplasias del Recto/patología , Imagen por Resonancia Magnética/métodos , Curva ROCRESUMEN
The organic solar cells based on halogen-free components, have been the new favorites to develop green and renewable energy. PBDB-T and its derivatives are considered the superior electron donors to construct the solar cells. Although there are plenty of researches about them, the charge-transfer mechanisms and excitation energy transfers of relative organic solar cells are still unclear, the developments of photovoltaic devices are restricted consequently. In this work, we calculate the electronic structures and excited-state properties of PBDB-T, PBT1-C, PBT1-O and PBT1-S donors in the gas phase from the many-body Green's function theory. With BTP-IC and BTP-IS as the acceptors, we consider the Förster, Dexter, and overlap electronic couplings to compute the excitation energy transfers of the dimers. The ionization energies and excited-state energies of the four donors calculated by GW + BSE are in good agreement with experiments, and they are sensitive to the functionals in the computation. We find two charge transfer schemes. The thienyl of PBDB-T molecule makes its charge-transfer state at the lowest energy, and the total electronic coupling of PBDB-T based dimer is the strongest. The Dexter, and overlap types electronic couplings are significant to study the excitation energy transfer of organic heterojunctions. We provide a theoretical guide in the design and synthesis of higher-performance halogen-free donors.
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PURPOSE: The adaptive immune responses induced by radiotherapy has been demonstrated to largely rely on STING-dependent type I interferons (IFNs) production. However, irradiated tumor cells often fail to induce dendritic cells (DCs) to produce type I IFNs. Hence, we aim to uncover the limitation of STING-mediated innate immune sensing following radiation, and identify efficient reagents capable to rescue the failure of type I IFNs induction for facilitating radiotherapy. METHODS: A targeted cell-based phenotypic screening was performed to search for active molecules that could elevate the production of type I IFNs. USP14 knockout or inhibition was assayed for IFN production and the activation of STING signaling in vitro. The mechanisms of USP14 were investigated by western blot and co-immunoprecipitation in vitro. Additionally, combinational treatments with PT33 and radiation in vivo and in vitro models were performed to evaluate type I IFNs responses to radiation. RESULTS: PT33 was identified as an enhancer of STING agonist elicited type I IFNs production to generate an elevated and durable STING activation profile in vitro. Mechanistically, USP14 inhibition or deletion impairs the deubiquitylation of K63-linked IRF3. Furthermore, blockade of USP14 with PT33 enhances DC sensing of irradiated-tumor cells in vitro, and synergizes with radiation to promote systemic antitumor immunity in vivo. CONCLUSION: Our findings reveal that USP14 is one of the major IFN production suppressors and impairs the activation of IRF3 by removing the K63-linked ubiquitination of IRF3. Therefore, blockage of USP14 results in the gain of STING signaling activation and radiation-induced adaptive immune responses.
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Inmunidad Adaptativa , Interferón Tipo I , Interferón beta , Radioterapia , Ubiquitina Tiolesterasa , Humanos , Inmunidad Innata , Factor 3 Regulador del Interferón , Interferón Tipo I/metabolismo , Interferón beta/metabolismo , Proteínas de la Membrana/metabolismo , Transducción de Señal , Células Tumorales CultivadasRESUMEN
OBJECTIVES: Accurate preoperative diagnosis of small cell neuroendocrine cancer of the cervix (SCNECC) is crucial for establishing the best treatment plan. This study aimed to develop an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information. METHODS: A total of 105 pathologically confirmed cervical cancer patients (35 SCNECC, 70 non-SCNECC) from multiple centres with complete clinical and MR records were included. Whole lesion histogram analysis of the ADC was performed. Multivariate logistic regression analysis was used to develop diagnostic models based on clinical, morphological, and histogram data. The predictive performance in terms of discrimination, calibration, and clinical usefulness of the different models was assessed. A nomogram for preoperatively discriminating SCNECC was developed from the combined model. RESULTS: In preoperative SCNECC diagnosis, the combined model, which had a diagnostic AUC (area under the curve) of 0.937 (95% CI: 0.887-0.987), outperformed the clinical-morphological model, which had an AUC of 0.869 (CI: 0.788-0.949), and the histogram model, which had an AUC of 0.872 (CI: 0.792-0.951). The calibration curve and decision curve analyses suggest that the combined model achieved good fitting and clinical utility. CONCLUSIONS: Non-invasive preoperative diagnosis of SCNECC can be achieved with high accuracy by integrating clinical, MR morphological, and ADC histogram features. The nomogram derived from the combined model can provide an easy-to-use clinical preoperative diagnostic tool for SCNECC. ADVANCES IN KNOWLEDGE: It is clear that the therapeutic strategies for SCNECC are different from those for other pathological types of cervical cancer according to V 1.2021 of the NCCN clinical practice guidelines in oncology for cervical cancer. This research developed an improved, non-invasive method for the preoperative diagnosis of SCNECC by integrating clinical, MR morphological, and apparent diffusion coefficient (ADC) information.
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Carcinoma Neuroendocrino , Carcinoma de Células Pequeñas , Neoplasias del Cuello Uterino , Femenino , Humanos , Nomogramas , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Cuello del Útero/patología , Imagen de Difusión por Resonancia Magnética/métodos , Carcinoma Neuroendocrino/diagnóstico por imagen , Carcinoma Neuroendocrino/cirugía , Estudios RetrospectivosRESUMEN
We provide the exact analytical form of diatomic molecular orbitals, as given by the solutions of a single-electron diatomic molecule with arbitrary nuclear charges, using our recently developed method for solving Schrödinger equations. We claim that the best representation of the wave function is a factorized form including a power prefactor, an exponentially decaying term, a modulator function on the exponential, and additional factors accounting for nodal surfaces and the magnetic quantum number. Applying our method, we have identified unexpected extreme points along the potential energy curves, hence revealing the limitations of the well-known concepts of bonding and antibonding.
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(1) Background and Objective: Major League Baseball (MLB) is one of the most popular international sport events worldwide. Many people are very interest in the related activities, and they are also curious about the outcome of the next game. There are many factors that affect the outcome of a baseball game, and it is very difficult to predict the outcome of the game precisely. At present, relevant research predicts the accuracy of the next game falls between 55% and 62%. (2) Methods: This research collected MLB game data from 2015 to 2019 and organized a total of 30 datasets for each team to predict the outcome of the next game. The prediction method used includes one-dimensional convolutional neural network (1DCNN) and three machine-learning methods, namely an artificial neural network (ANN), support vector machine (SVM), and logistic regression (LR). (3) Results: The prediction results show that, among the four prediction models, SVM obtains the highest prediction accuracies of 64.25% and 65.75% without feature selection and with feature selection, respectively; and the best AUCs are 0.6495 and 0.6501, respectively. (4) Conclusions: This study used feature selection and optimized parameter combination to increase the prediction performance to around 65%, which surpasses the prediction accuracies when compared to the state-of-the-art works in the literature.
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The generalized energy-based fragmentation (GEBF) approach is extended to facilitate ab initio investigations of structures, lattice energies, vibrational spectra and 1 H NMR chemical shifts of ionic crystals and condensed-phase ionic liquids (ILs) with the periodic boundary conditions (PBC). For selected periodic systems, our results demonstrate that the so-called PBC-GEBF approach can provide satisfactory descriptions on ground-state energies, structures, and vibrational spectra of ionic crystals and IL crystals. The PBC-GEBF approach is then applied to three realistic condensed phase systems. For three ionic crystals (LiCl, NaCl, and KCl), we apply the PBC-GEBF approach with MP2 theory as well as some popular DFT methods to investigate their crystal structures and lattice energies. Our calculations indicate that the crystal structures obtained with PBC-GEBF-MP2/6-311 + G** are very close to the corresponding X-ray structures, while PBC-GEBF-ωB97X-D/6-311 + G** provides satisfactory prediction for crystal structures and lattice energies. For two polymorphs of [n-C4 mim][Cl] crystals, we find that the PBC-GEBF approach at the M06-2X/6-311 + G** level can give a satisfactory descriptions on structures and Raman spectra of these two crystals. Furthermore, for [C2 mim][BF4 ] ILs, we demonstrate that their 1 H NMR chemical shifts can be estimated from averaging over 5 typical snapshots (extracted from MD simulations) with the PBC-GEBF approach at the B97-2/pcSseg-2 level. The calculated results account for the observed experimental data quite well. Therefore, we expect that the PBC-GEBF approach, combined with various quantum chemistry methods, will become an effective tool in predicting structures and properties of ionic crystals and condensed-phase ILs.
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The extensive applications of Firefly luciferase (Fluc) in numerous biological, biomedical, and clinical investigations rendered an urgent need for efficient and biocompatible Fluc inhibitors for the construction of novel assay platforms. Herein we describe the identification of 2-benzylidene-tetralone derivatives as highly potent and reversible Firefly luciferase inhibitors by competing with d-luciferin. The most active compound 48 was found to have >7000 fold higher potency (IC50 = 0.25 nM) than that of the well-known luciferase inhibitor resveratrol (IC50 = 1.9 µM) biochemically with sub- to low nanomolar IC50 values, and it can efficiently block the Fluc generated bioluminescence in vivo.
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Screening the lead compounds which could interact both with PAS and CAS of acetylcholinesterase (AChE) is an important trend in finding innovative drugs for Alzheimer's disease (AD). In this paper, four sesquiterpenes, i.e., atractylenolide III (1), atractylenolide IV (2), 3-acetyl-atractylon (3) and ß-eudesmol (4), were obtained from the wild Atractylode macrocephala grown in Qimen for the first time. Their structures were elucidated mainly by NMR spectroscopy. To screen the potential dual site inhibitors of AChE, the compounds 1, 2, 3, as well as a novel and rare bisesquiterpenoid lactone, biatractylenolide II (5), which was also obtained from the tilted plant in our previous investigation, were evaluated their AChE inhibitory activities by using Ellman's colorimetric method. The results showed that biatractylenolide II displayed moderate inhibitory activity (IC50 = 19.61 ± 1.11 µg/mL) on AChE. A further molecular docking study revealed that biatractylenolide II can interact with both the peripheral anionic site (PAS) and the catalytic active site (CAS) of AChE. These data suggest that biatractylenolide II can be considered a new lead compound to research and develop more potential dual site inhibitors of AChE.